Pharmaceutically active antibodies and other proteins are frequently formulated in liquid solutions, particularly for parenteral injection. The pharmaceutical composition may be sold commercially in a ready-to-use solution form or may be provided in a lyophilized form that is reconstituted with a liquid solution. Additional agents are often included in the protein solution to minimize degradation, precipitation and/or aggregation of the protein. Highly concentrated protein formulations are desirable when delivery of a therapeutic protein in small amounts of volume is required, e.g. during subcutaneous injection. However, highly concentrated protein solutions often exhibit increased viscosity. There exists a need to develop methods of reducing the viscosity of a formulation containing high concentrations of protein, and a need for resulting reduced viscosity formulations.
Creatine (also known as N-amidinosarcosine or (alpha-methylguanido)acetic acid) is a naturally occurring compound that is used by vertebrates for the purpose of energy storage in muscle cells. It is produced by the liver and kidneys and is present in meat and fish in high quantities. It is present in low amounts in blood and is converted in aqueous solutions to creatinine in a reversible reaction. The equilibrium ratio of creatine to creatinine (2-amino-1-methyl-2-imidazolin-4-one) depends on the pH of the solution and will be shifted towards creatinine formation at low pH.
Carnitine (also known as beta-hydroxy-gamma-(trimethylammonio)butyrate) is a metabolic co-factor that is essential for fatty acid metabolism in humans and other organisms. It is present in high amounts in meats and dairy products and in lower quantities in nuts, seeds, vegetables, fruits, and cereals.